The objective is to contribute to an overall understanding of the inter-relationships that exist between intrusive bacteria and host defense mechanisms. The present study concerns the interaction between Pseudomonas aeruginosa and the rat polymorphonuclear leukocyte (PMN). The approach focuses on the molecular basis for PMN antibacterial activity by examining the interaction of isolated antimicrobial substance derived from PMN granules with P. aeruginosa and other selected target bacteria. The experimental design is to obtain, fractionate, and purify the granule contents of rat PMN and then study the interaction of these components on bacteria in in vitro assay mixtures. The susceptibility of target bacteria will identify those fractions with antimicrobial potential. Lack of susceptibility to the killing fraction(s) by other bacteria with altered morphology or physiology will help identify these microbial factors that are responsible for resistance to the antimicrobial constituents. This type of information will contribute to a more thorough understanding of the inter-relationships that exist between host defense mechanisms and intrusive bacteria. Lung colonization/infection by Pseudomonas can be a major consideration in the clinical course of cystic fibrosis. During severe lung infection by Pseudomonas, the polymorphonuclear leukocyte (PMN) replaces the alveolar macrophage as the resident cell type. This large infiltration of polymorphonuclear leukocytes does not appear to be sufficiently capable of ingesting, destroying and removing the Pseudomonas bacteria. A study of this interaction between Pseudomonas and PMN may yield insight into the reasons why host defense mechanisms are thwarted during these infections. Many studies would be greatly facilitated by having an animal model system in which the clinical course of cystic fibrosis could be studied in detail. So far the rat appears to be the most promising animal for development of experiment cystic fibrosis. For this reason the present proposal will deal specifically with the rat leukocyte and its interaction with Pseudomonas. This type of study will yield insight into the reasons why Pseudomonas survives so well in cystic fibrosis patients.